This proposal is to request support for a Keystone Symposia meeting entitled "B Cells in Context", organized by Ann Marshak-Rothstein, Michael P. Cancro and Mark S. Schlissel, which will be held in Taos, New Mexico from February 24 - March 1, 2009. B lymphocytes play critical roles in immune responses by producing antibodies that eliminate pathogens, presenting antigens to T cells and secreting regulatory cytokines. B cells develop from hematopoietic precursors through stochastic and directed molecular events that include DNA rearrangements, epigenetic changes, and transcriptional regulation. Further differentiation is controlled by environmental factors that include interactions with hematopoietic and non-hematopoietic cells, pathogenic and non-pathogenic microorganisms, and a broad range of cytokines and chemokines. The B cell receptor repertoire is purged of self-specificity at multiple checkpoints prior to entrance into primary or memory pools. Failures in these processes can lead to autoimmune disease and lymphoid malignancy. These events involve highly choreographed cell-cell interactions and migratory behaviors. The goal of this meeting will be to ask how the various B cell microenvironments regulate the molecular events that determine B cell fate and function, and to explore how manipulation of the microenvironment can impact the immune response, autoimmunity, transformation and vaccine development.